Project Summary/Abstract Rare diseases (RD) and disorders collectively affect about 25 million Americans. RD research and care face common challenges, including: 1) insufficient knowledge about the etiology, pathophysiology, natural history and epidemiology of the diseases; 2) inadequate or non- uniform case definition and disease classification systems that make diagnosis and epidemiologic assessment difficult; 3) insufficient understanding of the determinants of multiple phenotypes and the relationships between genetic variance and phenotypic manifestations; 4) rarity and geographic dispersion of cases that hampers both access to qualified care and participation in research; 5) a dearth of clinically proven, safe and effective treatments; and 6) inadequate private investment into RD research and treatment. In the U.S., the Rare Diseases Act of 2002 authorizes the Office of Rare Disease Research to recommend a research agenda and promote coordination and cooperation among research programs. The Rare Diseases Clinical Research Consortia (RDCRC) that comprise the Rare Diseases Clinical Research Network (RDCRN) advance the diagnosis, management, and treatment of RDs to enhance clinical trial readiness. The RDCRN Data Management and Coordinating Center (DMCC) must provide state-of-the-art informatics, statistical and epidemiological expertise in clinical research study design and data management technology and processes, in order to guarantee the production of evidence that can support the progression of clinical and translational research (CTR) from Phase I through Phase III trials to adoption within standard clinical practice. To achieve the goal of enhancing clinical trial readiness throughout the RDCRN, we will establish the DMCC at Cincinnati Children?s and the University of Cincinnati with the following Specific Aims: 1): To advance the methods and the practice of RD CTR; 2) To develop and maintain a leading-edge, shared knowledge base for RD CTR; and 3) To establish the RDCRN as a globally connected resource for improving RD CTR across the entire RD ecosystem. We expect to accomplish these Aims by promoting collaboration and trial readiness, engaging patients and families, and creating an ?Esprit de Corps? for the RDCRN, through the adoption of Learning System principles. Our proposed DMCC brings a unique combination of world-class expertise, outstanding infrastructure, state-of-the-art technology and enthusiastic institutional support. This winning combination will accelerate scientific discovery and understanding across the network, which will bring new treatment options to trial, ultimately translating into improved health and wellness for RD patients and their families worldwide.